Gene Transfer Induced Hypercholesterolemia in Amyloid Mice

J Alzheimers Dis. 2018;65(4):1079-1086. doi: 10.3233/JAD-180494.

Abstract

A risk factor for cardiovascular disease (CVD), mutant PCSK9, was expressed in APP/PS1 mice to study the CVD-Alzheimer's disease inter-relationship. Cholesterol levels were elevated by 5-6-fold from 3 to 13 weeks after PCSK9 gene transfer. We tested whether hypercholesterolemia would increase amyloid-β plaques at a relatively early stage of plaque deposition. Plaque burden was increased in the hippocampus of PCSK9 treated mice though the increase was modest compared to the large elevation in cholesterol. Elevating cholesterol via gene transfer could be valuable in a variety of disease models compared to making crosses with germ-line transgenic mouse models of CVD.

Keywords: Adeno-associated virus; Alzheimer’s disease; PCSK9; amyloid-β plaques; cardiovascular disease; gene transfer; hypercholesterolemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Protein Precursor / genetics
  • Amyloidosis / genetics
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Cholesterol / blood*
  • Disease Models, Animal
  • Glial Fibrillary Acidic Protein / metabolism
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Hypercholesterolemia / etiology
  • Hypercholesterolemia / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins / metabolism
  • Mutation / genetics
  • Plaque, Amyloid / genetics*
  • Presenilin-1 / genetics
  • Proprotein Convertase 9 / genetics*
  • Proprotein Convertase 9 / metabolism*
  • Time Factors
  • Transduction, Genetic / methods*

Substances

  • Aif1 protein, mouse
  • Amyloid beta-Protein Precursor
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Microfilament Proteins
  • Presenilin-1
  • Green Fluorescent Proteins
  • Cholesterol
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9